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Objective: ESKALE is a French, multicentre, observational study of adults with treatment-resistant depression (TRD) treated with esketamine. This interim analysis describes baseline demographic and clinical characteristic evolution in patients included and treated from early access program to post-marketing launch., Methods: Data were collected from medical records and included patient characteristics, disease history at esketamine initiation, use of neurostimulation, the patient's care pathway, and the number of antidepressant treatment lines prescribed prior to esketamine initiation. Descriptive statistics were used for each cohort: the early access program 'Temporary Authorisation for Use' (ATU), post-ATU, and post-launch cohorts., Results: The overall ESKALE cohort ( N  = 160 included; n  = 157 treated with esketamine; average age 49.0 years; 66.2% female) demonstrated moderate-to-severe depression according to clinical assessment and a mean Montgomery-Åsberg Depression Rating Scale score of 32.6 (8.0); however, severity, subtype, and comorbidities were heterogeneous across the cohorts. Earlier use of esketamine and prior to alternative treatments occurred during the later cohorts., Conclusion: These findings demonstrated a high burden of TRD in these patients and that esketamine is used in TRD treatment regardless of their disease severity, subtype, or existing comorbidities. These results also suggest that esketamine is potentially a clinically useful alternative treatment, particularly with healthcare professionals gaining greater familiarity with and easier access to esketamine.

Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression are usually treatment-resistant, with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for treatment-resistant depression (TRD), but its efficacy on comorbid TRD-PTSD remains insufficiently documented. In particular, flashbacks can occur during esketamine administration and their influence on clinical outcomes is unknown., Objectives: Our main objective was to describe esketamine-induced traumatic flashbacks and their impact on clinical trajectories within a sample of patients with comorbid TRD-PTSD., Methods: We retrospectively collected clinical data of patients receiving esketamine nasal spray for TRD with comorbid PTSD who experienced at least one flashback of their trauma during esketamine sessions across 11 psychiatric departments., Results: Between February 2020 and March 2023, 22 adult patients with TRD met inclusion criteria. In sixteen patients (72.7%) flashbacks disappeared as the sessions progressed. In six patients (27.3%), esketamine treatment was stopped because of persistent flashbacks. When esketamine was continued, clinical response was observed both for depression and PTSD (depression response rate: 45.5% and remission rate: 22.7%; PTSD response rate: 45.5% and remission: 18.2%)., Limitations: The retrospective design of the study and the absence of a comparator group are the main limitations of our study., Conclusions: Our results suggest that the occurrence of esketamine-induced traumatic flashbacks does not hinder clinical response. On the contrary, when managed appropriately and combined with targeted psychotherapy, it could even contribute to positive outcomes., Competing Interests: Conflict of interest Most of the authors of this article received honoraria or consulting fees from Janssen-Cilag (MR, LM, MH, JH, SB, MD, EO, BG, AS, RG, RR, DZ, LS, OG, AL, LB) with no financial or other relationship relevant to the subject of this article.

Background: The efficacy of esketamine in treatment-resistant depression (TRD) has been confirmed. However, its administration is expensive and restrictive, with limited knowledge on how long the treatment should be continued. Predicting the treatment outcome would benefit patients and alleviate the global treatment cost. We aimed to define distinct trajectories of treatment response and assess their predictability., Methods: In this longitudinal study, two independent samples of patients with unipolar or bipolar TRD were treated with esketamine in real-world settings. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) before each esketamine administration. Latent class analyses were used to define trajectories of response., Results: In the original sample (N = 50), we identified two classes whose trajectories depicted response and non-response, respectively. The model was validated in the confirmatory sample (N = 55). Class membership was influenced by a few baseline characteristics such as concomitant benzodiazepine medication, number of depressive episodes or polarity. On the other hand, after only two esketamine administrations, the MADRS score predicted the 90-day trajectory of response with an accuracy of 80 %., Limitations: This observational study is not placebo-controlled. Therefore, its results and their generalizability need to be confirmed in experimental settings., Conclusions: After the first administrations of esketamine, the MADRS score has a good capacity to predict the most plausible trajectory of response. While thresholds and their predictive values need to be confirmed, this finding suggests that clinicians could base on MADRS scores their decision to discontinue treatment because of poor remaining chances of treatment response., Competing Interests: Declaration of competing interest PG received during the last 5 years fees for presentations at congresses or participation in scientific boards from Angelini, Janssen, Lundbeck, Otsuka and Viatris. ACP and PM received fees for presentations and congress participation from Janssen. RP has been invited by Janssen to a congress. LM has received honoraria or consulting fees from Bristol-Meyers-Squibb, Janssen, Servier, Lilly and Otsuka. RG has received compensation as a member of the scientific advisory board of Janssen, Lundbeck, Roche, SOBI, and Takeda, has served as a consultant and/or speaker for AstraZeneca, Boehringer Ingelheim, Pierre Fabre, Lilly, Lundbeck, LVMH, MAPREG, Novartis, Otsuka, Pileje, SANOFI, and Servier and received compensation. He has also received research support from Servier. FV has been invited to scientific meetings, consulted and/or served as a speaker, and received compensation from Lundbeck, Servier, Recordati, Janssen, Otsuka, LivaNova, Chiesi, and Rovi. He has received research support from LivaNova and Lundbeck. Other authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The phenomenon of malaise is on the rise at universities, reflecting a deteriorating psychological state that is a combination of anxiety and stress factors. This psychological and emotional upheaval within students is indicative of a fundamental existential issue. In fact, hidden behind the choice of an educational program is the significance given by the student to their life goals. It is this dimension of attributing meaning to one's education and, more broadly, to one's life (the existential dimension) that we have sought to explore. We hypothesized that a stable investment in one's life goals and a sense of psychological wellbeing during one's studies could be fostered by reflective work done alongside the educational process. Our research took the form of a mixed methodological approach to the attribution of meaning to education, including an interpretive phenomenological analysis (IPA), and the experimentation of support for the meaning of education. Four dimensions of meaning were found to be observable in varying degrees in all students, each playing a specific role. Moreover, this research has confirmed that the meaning of studies is not to be understood solely in terms of education, but is part of a singular life story. Reflective work, developing meaning, facilitated by others (advisor, teacher, etc.) can help preserve/restore the feeling of wellbeing. It should be noted that, as the work presented in this article predates the pandemic, we will not address the amplifying effects of this health crisis on existential issues, which some recent studies are beginning to highlight., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baatouche, de Maricourt and Bernaud.)

Major depressive disorder is a complex multifactorial condition with a so far poorly characterized underlying pathophysiology. Consequently, the available treatments are far from satisfactory as it is estimated that up to 30% of patients are resistant to conventional treatment. Recent comprehensive evidence has been accumulated which suggests that inflammation may be implied in the etiology of this disease. Here we investigated ketamine as an innovative treatment strategy due to its immune-modulating capacities. In a murine model of LPS-induced depressive-like behavior we demonstrated that a single dose of ketamine restores the LPS-induced depressive-like alterations. These behavioral effects are associated with i/ a reversal of anxiety and reduced self-care, ii/ a decrease in parenchymal cytokine production, iii/ a modulation of the microglial reactivity and iv/ a decrease in microglial quinolinic acid production that is correlated with plasmatic peripheral production. In a translational approach, we show that kynurenic acid to quinolinic acid ratio is a predictor of ketamine response in treatment-resistant depressed patients and that the reduction in quinolinic acid after a ketamine infusion is a predictor of the reduction in MADRS score. Our results suggest that microglia is a key therapeutic target and that quinolinic acid is a biomarker of ketamine response in major depressive disorder., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of -0.47 and -0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia., (Copyright © 2018. Published by Elsevier B.V.)

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery and quality of life. As the aging population grows, the rising number of elderly surgical patients has made PND an urgent clinical challenge. Despite increasing research efforts, the pathophysiological mechanisms underlying PND remain inadequately characterized, underscoring the need for a more integrated framework to guide targeted interventions. To better understand the molecular mechanisms and therapeutic targets of PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, and white matter lesions as central to PND pathophysiology, with particular parallels to encephalocele- and sepsis-associated cognitive impairments. Among these, neuroinflammation, mediated by pathways such as the NLRP3 inflammasome and blood–brain barrier disruption, emerges as a pivotal driver, triggering cascades that exacerbate neuronal injury. Oxidative stress and mitochondrial dysfunction synergistically amplify these effects, while neurotransmitter imbalances and microvascular alterations, including white matter lesions, contribute to synaptic dysfunction and cognitive decline. Anesthetic agents modulate these interconnected pathways, exhibiting both protective and detrimental effects. Propofol and dexmedetomidine demonstrate neuroprotective properties by suppressing neuroinflammation and microglial activation, whereas inhalational anesthetics like sevoflurane intensify oxidative stress and inflammatory responses. Ketamine, with its anti-inflammatory potential, offers promise but requires further evaluation to determine its long-term safety and efficacy. By bridging molecular insights with clinical practice, this review highlights the critical role of personalized anesthetic strategies in mitigating PND and improving cognitive recovery in elderly surgical patients. It aims to inform future research and clinical decision-making to address this multifaceted challenge. [ABSTRACT FROM AUTHOR]

Background: Research on the generalizability of clinical trials in panic disorder is limited. The present study sought to quantify the generalizability of clinical trials' results of individuals with DSM-IV panic disorder (PD) to a large community sample., Methods: Data were derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a large national representative sample of 43,093 adults of the United States population. We applied a standard set of eligibility criteria representative of PD clinical trials to all adults with past 12 months PD (n=907), and then to a subgroup of participants seeking treatment (n=105). Our aim was to determine the proportion of participants with PD who would have been excluded by typical eligibility criteria., Results: We found that more than 8 out of ten participants (80.52%; 95% CI=77.13-83.52%) with PD were excluded by at least one criterion. In the subgroup of participants who sought treatment, the exclusion rate by at least one criterion was higher (92.40%; 95% CI=84.60-96.42%). For the full sample and the treatment-seeking subsample, having currently a depression and a diagnosis of alcohol or drug abuse/dependence were the criteria excluding the highest percentage of participants. Having a lifetime history of bipolar disorder and a current significant medical condition also excluded a substantial proportion of individuals in both samples. Exclusion rates were similar when considering panic disorder with and without agoraphobia., Conclusions: Clinical trials, that exclude a majority of adults with panic disorder, should carefully consider the impact of eligibility criteria on the generalizability of their results. As required by CONSORT guidelines, reporting exclusion rate estimate and reasons of eligibility should be mandatory in both clinical trials and meta-analyses., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Tryptophan is widely present in foods such as peanuts, milk, and bananas, playing a crucial role in maintaining metabolic homeostasis in health and disease. Tryptophan metabolism is involved in the development and progression of immune, nervous, and digestive system diseases. Although some excellent reviews on tryptophan metabolism exist, there has been no systematic scientometric study as of yet. Methods: This review provides and summarizes research hotspots and potential future directions by analyzing annual publications, topics, keywords, and highly cited papers sourced from Web of Science spanning 1964 to 2022. Results: This review provides a scientometric overview of tryptophan metabolism disorder-triggered diseases, mechanisms, and therapeutic strategies. Conclusions: The gut microbiota regulates gut permeability, inflammation, and host immunity by directly converting tryptophan to indole and its derivatives. Gut microbial metabolites regulate tryptophan metabolism by activating specific receptors or enzymes. Additionally, the kynurenine (KYN) pathway, activated by indoleamine-2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase, affects the migration and invasion of glioma cells and the development of COVID-19 and depression. The research and development of IDO inhibitors help to improve the effectiveness of immunotherapy. Tryptophan metabolites as potential markers are used for disease therapy, guiding clinical decision-making. Tryptophan metabolites serve as targets to provide a new promising strategy for neuroprotective/neurotoxic imbalance affecting brain structure and function. In summary, this review provides valuable guidance for the basic research and clinical application of tryptophan metabolism. [ABSTRACT FROM AUTHOR]

Background. The efficacy and safety of esketamine nasal spray (ESK) were established in registration trials in patients with treatment‐resistant depression (TRD). This French real‐world study aimed to describe the treatment patterns, effectiveness, and safety of ESK in TRD patients over a 12‐month follow‐up. Materials and Methods. This study used secondary data from patient files of hospital‐based psychiatrists and started during the first French patient early access to ESK. The response and remission rates with ESK were analyzed using the total score of the Montgomery–Åsberg Depression Rating Scale (MADRS). The time to first treatment response and work resumption were described (Kaplan–Meier method). Adverse events (AEs) were analyzed. Results. Prior to ESK initiation, the 157 analyzed patients (age ≤ 65 years, 82.8%; female, 66.2%) had depression for 10.5 years (median, IQR, 4.2–21.2) and received a median of 6 (3–8) previous treatment lines. At ESK initiation, the mean ± SD total MADRS score was 32.1 ± 7.7. At that time, ESK was combined with antidepressants (93.6% of patients; SNRI, 65.0%; SSRI, 57.3%) and/or other potentiation strategy (63.1%; atypical antipsychotics, 36.3%; lithium, 25.6%; antiepileptics, 21.7%). During the 12‐month follow‐up, 125 patients (79.6%) discontinued ESK. The median duration of ESK treatment was 19.4 weeks (IQR, 4.4–40.1). At 1 month after ESK initiation, 40.2% of still treated patients met criteria for clinical response and 19.7% for remission (median time to response, 5.7 weeks; 95% CI (4.1–8.4)). 82.6% of active patients were on sick leave at ESK initiation; the work resumption rate was 24% (13%–40%) 12 weeks later. AEs were reported in 68.6% of patients, serious AEs in 17.2%, and AEs leading to ESK discontinuation in 14.6%. Conclusion. These real‐world effectiveness and safety data were consistent with findings from previous clinical trials, describing the real‐life clinical experience of patients receiving ESK and confirming that ESK has its place in therapy for the treatment of TRD. [ABSTRACT FROM AUTHOR]

The effects of general anesthetic agents (GAAs) on microglia and their potential neurotoxicity have attracted the attention of neuroscientists. Microglia play important roles in the inflammatory process and in neuromodulation of the central nervous system. Microglia-mediated neuroinflammation is a key mechanism of neurocognitive dysfunction during the perioperative period. Microglial activation by GAAs induces antiinflammatory and pro-inflammatory effects in microglia, suggesting that GAAs play a dual role in the mechanism of postoperative cognitive dysfunction. Understanding of the mechanisms by which GAAs regulate microglia may help to reduce the incidence of postoperative adverse effects. Here, we review the actions of GAAs on microglia and the consequent changes in microglial function. We summarize clinical and animal studies associating microglia with general anesthesia and describe how GAAs interact with neurons via microglia to further explore the mechanisms of action of GAAs in the nervous system. [ABSTRACT FROM AUTHOR]

Introduction: Depressive-like behavior has been shown to be associated with liver damage. This study aimed to evaluate the impact of three different models of depression on the behavior of mice with liver injury. Methods: During the 4 weeks of methionine/choline deficiency diet (MCD), adult C57BL/6 mice were randomly divided into four groups: MCD (no stress protocol, n = 6), chronic unpredictable mild stress (CUMS, n = 9), acute and repeated forced swim stress [aFSS (n = 9) and rFSS (n = 9)]. Results: All depression protocols induced increased anhedonia and anxiety-like behavior compared to baseline and had no impact on the severity of liver damage, according to ultrasonography. However, different protocols evoked different overall behavior patterns. After the depressive-like behavior induction protocols, animals subjected to aFSS did not exhibit anxiety-like behavior differences compared to MCD animals, while mice subjected to CUMS showed additional weight loss compared to FSS animals. All tested protocols for inducing depressive-like behavior decreased the short-term memory of mice with liver damage, as assessed by the novel object recognition test (NORT). Discussion: Our results show that the use of all protocols seems to generate different levels of anxiety-like behavior, but only the depressive-like behavior induction procedures associate additional anhedonia and memory impairment in mice with liver injury. [ABSTRACT FROM AUTHOR]

Aims: The N‐methyl‐D‐aspartate (NMDA) receptor (NMDAR) has been proven to be strongly correlated with rapid antidepressant effects. Here, GW043, as a new compound targeting NMDAR, we explored its antidepressant effects and its mechanism of action. Methods: Our study utilized electrophysiological techniques to confirm the effect of GW043 on NMDAR currents. Additionally, we assessed the selectivity of GW043 through high‐throughput receptor‐ligand binding experiments. The antidepressant properties of GW043 were examined using rodent behavioral models including the Forced Swim Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS). Mechanistic insight into GW043's onset was gained through western blot analysis, BrdU staining, Golgi staining, and electrophysiological techniques. Results: Electrophysiological studies indicated that GW043 acts as a partial agonist of NMDAR. Behavioral experiments confirmed the antidepressant effect of GW043 in rodents. Mechanistic investigations revealed that GW043 modulates synaptic plasticity through the LTP and BDNF‐mTOR pathways, consequently leading to an increase in the number of newborn neurons and subsequent antidepressant effects. Conclusion: Our findings disclose that GW043, as a partial agonist of NMDAR, can reverse depression‐like behaviors in rats by modulating synaptic plasticity, indicating its potential as an antidepressant agent. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a psychiatric condition characterized by sadness and anhedonia and is closely linked to chronic low-grade neuroinflammation, which is primarily induced by microglia. Nonetheless, the mechanisms by which microglia elicit depressive symptoms remain uncertain. This review focuses on the mechanism linking microglia and depression encompassing the breakdown of the blood-brain barrier, the hypothalamic-pituitary-adrenal axis, the gut-brain axis, the vagus and sympathetic nervous systems, and the susceptibility influenced by epigenetic modifications on microglia. These pathways may lead to the alterations of microglia in cytokine levels, as well as increased oxidative stress. Simultaneously, many antidepressant treatments can alter the immune phenotype of microglia, while anti-inflammatory treatments can also have antidepressant effects. This framework linking microglia, neuroinflammation, and depression could serve as a reference for targeting microglia to treat depression., Competing Interests: Declarations Ethics Approval Not applicable. Consent to Participate Not applicable. Consent for Publication Not applicable. Competing Interests The authors declare no competing interests. Disclaimer The funding organizations of this paper had no role in the design, article retrieval, writing, or the decision to submit the article for publication., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present study aims at identifying sleep patterns in insomnia in a clinical sample using three strategies to define poor nights. Sleep diaries and self-reported questionnaires were collected from 77 clinical patients with insomnia. The conditional probabilities of observing a poor night after 1, 2, or 3 consecutive poor nights were computed according to three strategies with same criteria for sleep onset latency, wake after sleep onset, and sleep efficiency, but varying criterion for total sleep time. Latent profile analyses were conducted to derive sleep patterns. Uni- and multivariate analyses were conducted to characterise the sleep patterns identified. A total of 1586 nights were analysed. The strategy used significantly influenced the average percentage of reported poor nights. Two to three sleep patterns were derived per strategy. Within each strategy, sleep patterns differed from each other on sleep variables and night-to-night variability. Results suggest the existence of sleep patterns in insomnia among individuals consulting in psychological clinics. Adding a total sleep time of 6-h cut-off as a criterion to define poor nights increases the accuracy of the strategy to define poor night and allows to identify sleep patterns of poor nights in insomnia., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Résumé Relativement peu connue en psychiatrie, la médecine thermale psychiatrique est une approche originale qui commence à faire l'objet d'évaluations rigoureuses. Depuis les années 2000, elle a fait l'objet d'études qui en ont mieux montré les contours et les potentiels domaines d'application. Située à l'interface de la médecine générale et de la psychiatrie, entre la médecine ambulatoire et la médecine hospitalière, la médecine thermale s'adresse essentiellement aux troubles anxieux, aux troubles réactionnels, adaptatifs, et à des situations cliniques telles que le sevrage de benzodiazépines ou la psychoéducation. À base de balnéothérapie, celle-ci est basée sur la qualité de la relation entre le médecin et le patient, sur la mise en place d'un environnement médicalisé, structurant, anxiolytique et a développé des modèles de prise en charge psychoéducatifs inspirés des thérapies cognitives et comportementales. En 2010, la preuve de l'efficacité de la crénothérapie a été apportée dans la prise en charge des troubles anxieux généralisés sur une durée de deux mois. En 2016, une autre étude a permis de démontrer l'intérêt de la balnéothérapie en cure thermale pour réaliser le sevrage de benzodiazépines chez les patients anxieux, consommateurs chroniques et motivés pour l'arrêt. Parallèlement, la balnéothérapie a été évaluée dans les troubles affectifs de pathologies douloureuses chroniques, en particulier de la fibromyalgie. Une autre étude a démontré son intérêt dans la prise en charge du burn-out. Nous résumons ici les résultats de ces principaux travaux. Abstract Objectives Relatively little known in psychiatry, spa psychiatric medicine is an original approach, which has started to form the subject of thorough assessments. It concerns 3 week spa therapy stays in practice, the patient being totally free and self-sufficient, though having to go to 3 to 4 prescribed daily bathing sessions and to the medical and psychotherapy follow-up provided within the scope of their medical care. Since the beginning of the years 2000, Spa Medicine has been subject to studies that have better shown the outline and its potential application areas. We present you here, through a review of the literature from these past 30 years, the main elements of scientific proof of its therapeutic activity and as a result, its best documented indications in psychiatry. Therefore, the article is stated by chapter, indication by indication. Results The area which brings the best level of proof relates to generalised anxiety disorder. One study called STOP-TAG (Dubois O, Salomon R, Germain C, et al. 2010) (Salamon R, Germain C, Olié JP, Dubois O, 2008) supervised by 2 Inserm units: ISPED in Bordeaux II and Sainte-Anne, brought the proof of a superior efficacy of the therapy compared to Paroxetine over a period of 8 weeks (5 weeks after the end of the course of treatment). This result is supported by other less thorough works that all feed the first initial study. As a consequence, an Austrian study became interested in the effects of spa bathing observed over 3 weeks in burn-out situations. The results show the efficacy of this medical care at the end of the treatment and 3 months afterwards. Subsequently, the interest in a psycho-educative programme carried out in spa therapy for anxiety patients and chronic benzodiazepine consumers, was studied in addiction. The SPECTh study (De Maricourt P, Gorwood P, Hergueta T, Dubois O. et al. 2016) allowed to follow 70 patients, therapeutically stable and motivated in their stopping. Six months after their treatment, 41.42 % of these patients had ceased all consumption and 80 % had reduced by half, whereas 16 % were in a position of therapeutic failure. This area of addiction has not been subject to other studies particularly concerning excessive alcohol consumption or of ta (the indication of which seems by the way less obvious) or tobacco. If few studies have sought to evaluate the significance of Spa Medicine in depressive disorders, many works have brought out the doubtless indirect impact of this practice on reactional depressive states, especially painful chronic states and on a generalised anxiety state. Likewise, it is above all the spa rheumatologists' works that have brought solid proof of the efficacy of spa therapy and bathing in affective disorders (anxiety, depressive disorder) associated with painful chronic states (fibromyalgia, chronic low back pain, after breast cancer...). As far as the mechanism of action is concerned, numerous hypotheses exist. This is not the place to present them all. However, the result of an original and important pre-study is presented here that highlights the interest of an optimal "letting go" as statistical indicator of a clinical improvement of anxiety in the long run. If the notion of letting go remains to be defined scientifically, it comprises a notion of non-resistance, the giving up of the patient's will to want to control the events, which makes this therapy different from psychological approaches, that are more intellectual directing the patient towards a mastery effort and self and thought control. This specificity in the spa approach by "non-mastered giving up" of its defences and by returning to self, thanks to the taking up again of pleasant physical sensations, often forgotten, seems to be one of the forms of action, psychologically and fundamentally in spa therapy. Conclusion Situated at the interface of general medicine and psychiatry, and between ambulatory medicine and hospital medicine, spa medicine is therefore essentially intended for anxiety disorders, adapting reactional disorders and clinical situations such as severance from Benzodiazepines or psycho-education. Centred on the spa bathing practice, it is also based on the quality of the relation between doctor and patient, on the setting up of a structuring, anxiolytic medicalised environment. Furthermore, these past few years, examples of psycho-educative medical care inspired from cognitive and behavioural therapies have been developed at the heart of the " psy spa resorts". It is important to appreciate the effort carried out by these spa centres, far away from schools of medicine, that make the effort of bringing thorough scientific proof validating their interest in psychiatry, what is more in areas (anxiety, Benzodiazepine severance, chronic pain, burn-out...) where solutions and therapeutic alternatives are not exactly legion. [ABSTRACT FROM AUTHOR]

Spa therapy (aka crenobalneotherapy) has been the object of criticism due to insufficient evidence of its effectiveness. While further effectiveness studies are needed, others are also required to better evaluate the curative factors involved during spa therapy that may contribute to the effectiveness. The current study used specific scales to investigate two possible curative factors: the psychosomatic state and the letting-go of patients with mental disorders after 3 weeks of spa therapy. The Saujon Psychosomatic Questionnaire (SPQ) and the Quantified Assessment of Fluidity of Consciousness Questionnaire (QACF) evaluate psychosomatic state and letting-go, respectively. The Hospital Anxiety and Depression Scale (HAD) and the Insomnia Severity Index (ISI) evaluate depression and anxiety symptoms and insomnia symptoms, respectively. Sixty-five subjects (57 women (87.69%); 8 men), with a mean age of 56.9 (± 9.7) years, were included. SPQ and QAFC scores improved significantly before and after the 3 weeks of spa therapy. Improvement in HAD and ISI scores was significantly correlated with SPQ and QACF scores. These preliminary results suggest that the induced psychosomatic state and the letting-go induced by spa treatment with bubbling baths, jet showers, pool bathing and massage could help patients to become more available and more able to change their psychophysiological state. [ABSTRACT FROM AUTHOR]

Spa therapy is a medical treatment based on the use of natural mineral water. In France, spa therapy is delivered in spa care facilities (SCF) involving the intervention of several actors (stakeholders). Spa doctors are key stakeholders as they prescribe the treatments, follow spa patients and assess spa therapy with scientific studies. This study aimed to analyze the spa doctors' relationships in order to highlight their role in transferring information to other stakeholders, particularly to spa managers. For that purpose, we used the social network analysis (SNA) method by means of snowball data collection. We sent a questionnaire to all the spa therapy categories of actors. In total, 80 persons answered and declared 397 relationships. Our results, based on the categorization of respondents and of their relationships and on quantitative indicators (density, response rate), show that spa doctors demonstrate a very acceptable density of relations with spa managers and elected local authorities. However, they appear to be poorly involved in relations concerning the strategy and management of SCF, although they are essential actors in ensuring the medical relevance and sustainability of spa therapy. This research is of interest to patients' care as it recommends deeper involvement of spa doctors in the management of SCF in order to optimize access to informational resources, specifically regarding the evolution of treatments in accordance with scientific progress. Our data are of international scope because the organizational model of balneotherapy, based on the cooperation between spa doctors and SCF, is universal. [ABSTRACT FROM AUTHOR]

Prior studies report conflicting results about the association between lithium use and all-cause mortality. In addition, data are scarce on this association among older adults with psychiatric disorders. In this report, we sought to examine the associations of lithium use with all-cause mortality and specific causes of death (i.e., due to cardiovascular disorder, non-cardiovascular disease, accident, or suicide) among older adults with psychiatric disorders during a 5-year follow-up period. In this observational epidemiological study, we used data from 561 patients belonging to a Cohort of individuals with Schizophrenia or Affective disorders aged 55-years or more (CSA). Patients taking lithium at baseline were first compared to patients not taking lithium, and then to patients taking (i) antiepileptics and (ii) atypical antipsychotics in sensitivity analyses. Analyses were adjusted for socio-demographic (e.g., age, gender), clinical characteristics (e.g., psychiatric diagnosis, cognitive functioning), and other psychotropic medications (e.g. benzodiazepines). There was no significant association between lithium use and all-cause mortality [AOR=1.12; 95%CI=0.45-2.79; p=0.810] or disease-related mortality [AOR=1.37; 95%CI=0.51-3.65; p=0.530]. None of the 44 patients taking lithium died from suicide, whereas 4.0% (N=16) of patients not receiving lithium did. These findings suggest that lithium may not be associated with all-cause or disease-related mortality and might be associated with reduced risk of suicide in this population. They argue against the underuse of lithium as compared with antiepileptics and atypical antipsychotics among older adults with mood disorders. [ABSTRACT FROM AUTHOR]

Well-being associated with optimism, social support, and self-esteem is positively correlated with career decision. In this perspective, a rather recent concept of flourishing as an integrative notion incorporating these different resources, positive affect, and positive experience is particularly relevant to better understand the relations and correlations between self-evaluation, well-being, and career decision-making difficulties. The present study then examines the relationship between these possible difficulties, self-esteem, self-efficacy, and flourishing. One hundred and seventy-two higher education students participated in the study and completed a four-part questionnaire with the Career Decision-Making Difficulties Questionnaire, the Flourishing Scale, the Rosenberg Self-esteem Scale, and the General Self-Efficacy Scale. The results highlight the mediation of psychological flourishing between personality dimensions—self-esteem and self-efficacy—and career decision difficulties and the fact that those who are most flourishing in their lives will also have the least difficulty in making a career decision. As for the practical implications, guidance counselors for students and young adults need to identify resources and difficulties they have to cope with. This study emphasizes the importance of guiding students in three areas: self-esteem, the perceived quality of social relations, and the meaning attributed to one's existence. Finally, the contribution of positive psychology to career development will be discussed. [ABSTRACT FROM AUTHOR]

In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up to 27% of patients with MDD and is associated with a more severe, chronic, and treatment-resistant trajectory. Inflammation is not unique to depression and has transdiagnostic effects suggesting a shared etiological risk factor underlying psychopathologies and metabolic disorders. Research supports an association but not necessarily a causation with depression. Putative mechanisms link chronic stress to dysregulation of the HPA axis and immune cell glucocorticoid resistance resulting in hyperactivation of the peripheral immune system. The chronic extracellular release of DAMPs and immune cell DAMP-PRR signaling creates a feed forward loop that accelerates peripheral and central inflammation. Higher plasma levels of inflammatory cytokines, most consistently interleukin IL-1β, IL-6, and TNF-α, are correlated with greater depressive symptomatology. Cytokines sensitize the HPA axis, disrupt the negative feedback loop, and further propagate inflammatory reactions. Peripheral inflammation exacerbates central inflammation (neuroinflammation) through several mechanisms including disruption of the blood-brain barrier, immune cellular trafficking, and activation of glial cells. Activated glial cells release cytokines, chemokines, and reactive oxygen and nitrogen species into the extra-synaptic space dysregulating neurotransmitter systems, imbalancing the excitatory to inhibitory ratio, and disrupting neural circuitry plasticity and adaptation. In particular, microglial activation and toxicity plays a central role in the pathophysiology of neuroinflammation. Magnetic resonance imaging (MRI) studies most consistently show reduced hippocampal volumes. Neural circuitry dysfunction such as hypoactivation between the ventral striatum and the ventromedial prefrontal cortex underlies the melancholic phenotype of depression. Chronic administration of monoaminebased antidepressants counters the inflammatory response, but with a delayed therapeutic onset. Therapeutics targeting cell mediated immunity, generalized and specific inflammatory signaling pathways, and nitro-oxidative stress have enormous potential to advance the treatment landscape. Future clinical trials will need to include immune system perturbations as biomarker outcome measures to facilitate novel antidepressant development. In this overview, we explore the inflammatory correlates of depression and elucidate pathomechanisms to facilitate the development of novel biomarkers and therapeutics. [ABSTRACT FROM AUTHOR]

Sepsis-associated encephalopathy (SAE) remains a challenge for intensivists that is exacerbated by lack of an effective diagnostic tool and an unambiguous definition to properly identify SAE patients. Risk factors for SAE development include age, genetic factors as well as pre-existing neuropsychiatric conditions. Sepsis due to certain infection sites/origins might be more prone to encephalopathy development than other cases. Currently, ICU management of SAE is mainly based on non-pharmacological support. Pre-clinical studies have described the role of the alarmin high mobility group box 1 (HMGB1) in the complex pathogenesis of SAE. Although there are limited data available about the role of HMGB1 in neuroinflammation following sepsis, it has been implicated in other neurologic disorders, where its translocation from the nucleus to the extracellular space has been found to trigger neuroinflammatory reactions and disrupt the blood–brain barrier. Negating the inflammatory cascade, by targeting HMGB1, may be a strategy to complement non-pharmacologic interventions directed against encephalopathy. This review describes inflammatory cascades implicating HMGB1 and strategies for its use to mitigate sepsis-induced encephalopathy. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a common mental illness characterized by persistent low mood and anhedonia, normally accompanied with cognitive impairment. Due to its rising incidence and high rate of recurrence and disability, MDD poses a substantial threat to patients' physical and mental health, as well as a significant economic cost to society. However, the etiology and pathogenesis of MDD are still unclear. Chronic inflammation may cause indoleamine-2,3-dioxygenase (IDO) to become overactive throughout the body and brain, resulting in excess quinolinic acid (QUIN) and less kynuric acid (KYNA) in the brain. QUIN's neurotoxicity damages glial cells and neurons, accelerates neuronal apoptosis, hinders neuroplasticity, and causes depression due to inflammation. Therefore, abnormal TRP-KYN metabolic pathway and its metabolites have been closely related to MDD, suggesting changes in the TRP-KYN metabolic pathway might contribute to MDD. In addition, targeting TRP-KYN with traditional Chinese medicine showed promising treatment effects for MDD. This review summarizes the recent studies on the TRP-KYN metabolic pathway and its metabolites in depression, which would provide a theoretical basis for exploring the etiology and pathogenesis of depression. [ABSTRACT FROM AUTHOR]

Delirium, a common form of acute brain dysfunction, is associated with increased morbidity and mortality, especially in older patients. The underlying pathophysiology of delirium is not clearly understood, but acute systemic inflammation is known to drive delirium in cases of acute illnesses, such as sepsis, trauma, and surgery. Based on psychomotor presentations, delirium has three main subtypes, such as hypoactive, hyperactive, and mixed subtype. There are similarities in the initial presentation of delirium with depression and dementia, especially in the hypoactive subtype. Hence, patients with hypoactive delirium are frequently misdiagnosed. The altered kynurenine pathway (KP) is a promising molecular pathway implicated in the pathogenesis of delirium. The KP is highly regulated in the immune system and influences neurological functions. The activation of indoleamine 2,3-dioxygenase, and specific KP neuroactive metabolites, such as quinolinic acid and kynurenic acid, could play a role in the event of delirium. Here, we collectively describe the roles of the KP and speculate on its relevance in delirium. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) is a prevalent clinical entity following surgery and is characterized by declined neurocognitive function. Neuroinflammation mediated by microglia is the essential mechanism of POCD. Anesthetics are thought to be a major contributor to the development of POCD, as they promote microglial activation and induce neuroinflammation. However, this claim remains controversial. Anesthetics can exert both anti- and proinflammatory effects by modulating microglial activation, suggesting that anesthetics may play dual roles in the pathogenesis of POCD. Here, we review the mechanisms by which the commonly used anesthetics regulate microglial activation via inflammatory signaling pathways, showing both anti- and proinflammatory properties of anesthetics, and indicating how perioperative administration of anesthetics might either relieve or worsen POCD development. The potential for anesthetics to enhance cognitive performance based on their anti-inflammatory properties is further discussed, emphasizing that the beneficial effects of anesthetics vary depending on dose, exposure time, and patients’ characteristics. To minimize the incidence of POCD, we recommend considering these factors to select appropriate anesthetics. [ABSTRACT FROM AUTHOR]

Treatment-resistant depression is a pleomorphic phenomenon occurring in 30% of patients with depression. The chance to achieve remission decreases with every subsequent episode. It constitutes a significant part of the global disease burden, causes increased morbidity and mortality, and is associated with poor quality of life. It involves multiple difficult-to-treat episodes, with increasing resistance over time. The concept of staging captures the process of changes causing increasing treatment resistance and global worsening of functioning in all areas of life. Ketamine is a novel rapid-acting antidepressant with neuroplastic potential. Here, we argue that ketamine use as an add-on treatment of resistant major depressive disorder, based on its unique pharmacological properties, can reverse this process, give hope to patients, and prevent therapeutic nihilism. [ABSTRACT FROM AUTHOR]